| Autor: |
Weili Miao, Douglas F. Porter, Vanessa Lopez-Pajares, Zurab Siprashvili, Robin M. Meyers, Yunhao Bai, Duy T. Nguyen, Lisa A. Ko, Brian J. Zarnegar, Ian D. Ferguson, Matthew M. Mills, Christie E. Jilly-Rehak, Cheng-Guo Wu, Yen-Yu Yang, Jordan M. Meyers, Audrey W. Hong, David L. Reynolds, Muthukumar Ramanathan, Shiying Tao, Sizun Jiang, Ryan A. Flynn, Yinsheng Wang, Garry P. Nolan, Paul A. Khavari |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cell. 186(1) |
| ISSN: |
1097-4172 |
| Popis: |
Glucose is a universal bioenergy source; however, its role in controlling protein interactions is unappreciated, as are its actions during differentiation-associated intracellular glucose elevation. Azido-glucose click chemistry identified glucose binding to a variety of RNA binding proteins (RBPs), including the DDX21 RNA helicase, which was found to be essential for epidermal differentiation. Glucose bound the ATP-binding domain of DDX21, altering protein conformation, inhibiting helicase activity, and dissociating DDX21 dimers. Glucose elevation during differentiation was associated with DDX21 re-localization from the nucleolus to the nucleoplasm where DDX21 assembled into larger protein complexes containing RNA splicing factors. DDX21 localized to specific SCUGSDGC motif in mRNA introns in a glucose-dependent manner and promoted the splicing of key pro-differentiation genes, including GRHL3, KLF4, OVOL1, and RBPJ. These findings uncover a biochemical mechanism of action for glucose in modulating the dimerization and function of an RNA helicase essential for tissue differentiation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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